S3 guideline Allergy Prevention.

BACKGROUND: The persistently high prevalence of allergic diseases in Western industrial nations and the limited possibilities of causal therapy make evidence-based recommendations for primary prevention necessary. METHODS: The recommendations of the S3 guideline Allergy Prevention, published in its last version in 2014, were revised and consulted on the basis of a current systematic literature search. The evidence search was conducted for the period 06/2013 - 11/2020 in the electronic databases Cochrane and MEDLINE, as well as in the reference lists of current reviews and through references from experts. The literature found was screened in two filtering processes, first by title and abstract, and the remaining papers were screened in the full text for relevance. The studies included after this were sorted by level of evidence, and the study quality was indicated in terms of potential bias (low/high). The revised recommendations were formally agreed and consented upon with the participation of representatives of the relevant professional societies and (self-help) organizations (nominal group process). Of 5,681 hits, 286 studies were included and assessed. RESULTS: Recommendations on maternal nutrition during pregnancy and breastfeeding as well as on infant nutrition in the first months of life again play an important role in the updated guideline: Many of the previous recommendations were confirmed by the current data. It was specified that breastfeeding should be exclusive for the first 4 - 6 months after birth, if possible, and that breastfeeding should continue with the introduction of complementary foods. A new recommendation is that supplementary feeding of cow's milk-based formula should be avoided in the first days of life if the mother wishes to breastfeed. Furthermore, it was determined that the evidence for a clear recommendation for hydrolyzed infant formula in non-breastfed infants at risk is currently no longer sufficient. It is therefore currently recommended to check whether an infant formula with proven efficacy in allergy prevention studies is available until the introduction of complementary feeding. Finally, based on the EAACI guideline, recommendations were made for the prevention of chicken egg allergy by introducing and regularly giving thoroughly heated (e.g., baked or hard-boiled) but not "raw" chicken egg (also no scrambled egg) with the complementary food. The recommendation to introduce peanut in complementary feeding was formulated cautiously for the German-speaking countries: In families who usually consume peanut, the regular administration of peanut-containing foods in age-appropriate form (e.g., peanut butter) with the complementary diet can be considered for the primary prevention of peanut allergy in infants with atopic dermatitis (AD). Before introduction, a clinically relevant peanut allergy must be ruled out, especially in infants with moderate to severe AD. There is still insufficient evidence for an allergy-preventive efficacy of prebiotics or probiotics, vitamin D, or other vitamins in the form of supplements so that recommendations against their supplementation were adopted for the first time in the current guideline. Biodiversity plays an important role in the development of immunological tolerance to environmental and food allergens: there is clear evidence that growing up on a farm is associated with a lower risk of developing asthma and allergic diseases. This is associated with early non-specific immune stimulation due to, among other things, the greater microbial biodiversity of house dust in this habitat. This aspect is also reflected in the recommendations on animal husbandry, on which a differentiated statement was made: In families without a recognizable increased allergy risk, pet keeping with cats or dogs should not generally be restricted. Families with an increased allergy risk or with children with already existing AD should not acquire a new cat - in contrast, however, dog ownership should not be discouraged. Interventions to reduce exposure to dust mite allergens in the home, such as the use of mite allergen-proof mattress covers ("encasings"), should be restricted to patients with already proven specific sensitization against house dust mite allergen. Children born by caesarean section have a slightly increased risk of asthma - this should be taken into account when advising on mode of delivery outside of emergency situations. Recent work also supports the recommendations on air pollutants: Active and passive exposure to tobacco smoke increase the risk of allergies, especially asthma, and should therefore be avoided. Exposure to nitrogen oxides, ozone, and small particles (PM 2.5) is associated with an increased risk, especially for asthma. Therefore, exposure to emissions of nitrogen oxides, ozone, and small particles (PM 2.5) should be kept low. The authors of this guideline are unanimously in favor of enacting appropriate regulations to minimize these air pollutants. There is no evidence that vaccinations increase the risk of allergies, but conversely there is evidence that vaccinations can reduce the risk of allergies. All children, including children at risk, should be vaccinated according to the current recommendations of the national public health institutes, also for reasons of allergy prevention. CONCLUSION: The consensus of recommendations in this guideline is based on an extensive evidence base. The update of the guideline enables evidence-based and up-to-date recommendations for the prevention of allergic diseases including asthma and atopic dermatitis.

Allergen extract- and component-based diagnostics in children of the ALLIANCE asthma cohort.

BACKGROUND: Current in vitro allergen-specific IgE (sIgE) detection assays measure IgE against allergen extracts or molecules in a single- or multiplex approach. Direct comparisons of the performance of such assays among young children with common presentations of allergic diseases regardless of sensitization status are largely missing. OBJECTIVES: The aim of this study was a comparison of the analytical and diagnostic performance for common clinical questions of three commonly used technologies which rely upon different laboratory methodologies among children of the All Age Asthma (ALLIANCE) cohort (clinicaltrials.gov: NCT02496468). METHODS: Sera from 106 paediatric study participants (mean age 4 years) were assessed for the presence of sIgE by means of the ImmunoCAP™ sx1 and fx5 mixes, the ImmunoCAP ISAC™ 112 microarray and a Euroline™ panel. RESULTS: Total and negative concordance was high (>82%->89%), while positive concordance varied considerably (0%-100%) but was also >50% for the most common sensitizations analysed (house dust mite and birch). All three test systems showed good sensitivity and specificity (AUC consistently > 0.7). However, no significant differences with regard to identifying sIgE sensitizations associated with symptoms in children with suspected pollen- or dust-triggered wheeze or presenting with symptoms of allergic rhinoconjunctivitis or food allergy were detected. Extending the number of allergens did not change the similar performance of the three assay systems. CONCLUSION AND CLINICAL RELEVANCE: Among young children, the three sIgE assays showed good analytical and diagnostic concordance. Our results caution that the identification of larger numbers of sensitizations by more comprehensive multiplex approaches may not improve the clinical utility of sIgE testing in this age group.

Excessive Unbalanced Meat Consumption in the First Year of Life Increases Asthma Risk in the PASTURE and LUKAS2 Birth Cohorts.

A higher diversity of food items introduced in the first year of life has been inversely related to subsequent development of asthma. In the current analysis, we applied latent class analysis (LCA) to systematically assess feeding patterns and to relate them to asthma risk at school age. PASTURE (N=1133) and LUKAS2 (N=228) are prospective birth cohort studies designed to evaluate protective and risk factors for atopic diseases, including dietary patterns. Feeding practices were reported by parents in monthly diaries between the 4th and 12th month of life. For 17 common food items parents indicated frequency of feeding during the last 4 weeks in 4 categories. The resulting 153 ordinal variables were entered in a LCA. The intestinal microbiome was assessed at the age of 12 months by 16S rRNA sequencing. Data on feeding practice with at least one reported time point was available in 1042 of the 1133 recruited children. Best LCA model fit was achieved by the 4-class solution. One class showed an elevated risk of asthma at age 6 as compared to the other classes (adjusted odds ratio (aOR): 8.47, 95% CI 2.52-28.56, p = 0.001) and was characterized by daily meat consumption and rare consumption of milk and yoghurt. A refined LCA restricted to meat, milk, and yoghurt confirmed the asthma risk effect of a particular class in PASTURE and independently in LUKAS2, which we thus termed unbalanced meat consumption (UMC). The effect of UMC was particularly strong for non-atopic asthma and asthma irrespectively of early bronchitis (aOR: 17.0, 95% CI 5.2-56.1, p < 0.001). UMC fostered growth of iron scavenging bacteria such as Acinetobacter (aOR: 1.28, 95% CI 1.00-1.63, p = 0.048), which was also related to asthma (aOR: 1.55, 95% CI 1.18-2.03, p = 0.001). When reconstructing bacterial metabolic pathways from 16S rRNA sequencing data, biosynthesis of siderophore group nonribosomal peptides emerged as top hit (aOR: 1.58, 95% CI 1.13-2.19, p = 0.007). By a data-driven approach we found a pattern of overly meat consumption at the expense of other protein sources to confer risk of asthma. Microbiome analysis of fecal samples pointed towards overgrowth of iron-dependent bacteria and bacterial iron metabolism as a potential explanation.

Exposure to nonmicrobial N-glycolylneuraminic acid protects farmers' children against airway inflammation and colitis.

BACKGROUND: Childhood exposure to a farm environment has been shown to protect against the development of inflammatory diseases, such as allergy, asthma, and inflammatory bowel disease. OBJECTIVE: We sought to investigate whether both exposure to microbes and exposure to structures of nonmicrobial origin, such as the sialic acid N-glycolylneuraminic acid (Neu5Gc), might play a significant role. METHODS: Exposure to Neu5Gc was evaluated by quantifying anti-Neu5Gc antibody levels in sera of children enrolled in 2 farm studies: the Prevention of Allergy Risk factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle (PARSIFAL) study (n = 299) and the Protection Against Allergy Study in Rural Environments (PASTURE) birth cohort (cord blood [n = 836], 1 year [n = 734], 4.5 years [n = 700], and 6 years [n = 728]), and we associated them with asthma and wheeze. The effect of Neu5Gc was examined in murine airway inflammation and colitis models, and the role of Neu5Gc in regulating immune activation was assessed based on helper T-cell and regulatory T-cell activation in mice. RESULTS: In children anti-Neu5Gc IgG levels correlated positively with living on a farm and increased peripheral blood forkhead box protein 3 expression and correlated inversely with wheezing and asthma in nonatopic subjects. Exposure to Neu5Gc in mice resulted in reduced airway hyperresponsiveness and inflammatory cell recruitment to the lung. Furthermore, Neu5Gc administration to mice reduced the severity of a colitis model. Mechanistically, we found that Neu5Gc exposure reduced IL-17+ T-cell numbers and supported differentiation of regulatory T cells. CONCLUSIONS: In addition to microbial exposure, increased exposure to non-microbial-derived Neu5Gc might contribute to the protective effects associated with the farm environment.